Boston, MA - Results from the Massachusetts stent registry—suggesting that drug-eluting stents (DES) reduce two-year mortality in acute MI patients, as compared with bare-metal stents—have now been published in the New England Journal of Medicine [1]. The results were first presented during the ACC 2008 meeting, as reported by heartwire.

"Until now, the rates of use of DES have been significantly lower in patients with [ST-segment-elevation MI] STEMI than in the overall patient population, even in my own institution, where we use DES for the large majority of procedures," first author on the study, Dr Laura Mauri (Brigham and Women's Hospital, Boston, MA), told heartwire. "We now can be more confident that, in patients who can take antiplatelet therapy, DES are safe in patients with STEMI or non-STEMI, are associated with a reduction in target-vessel revascularization, and may even be associated with improved survival."

In all, the registry included 7217 patients treated for acute MI between April 1, 2003 and September 30, 2004: 4016 were treated with DES, while 3201 patients received bare-metal stents. Unadjusted rates of death, MI, and repeat PCI at two years were significantly lower in the DES-treated patients than in the bare-metal-stent-treated patients. Using propensity-score matching, based on 63 variables, to minimize the risk of selection bias, investigators came up with 2570 AMI patients treated with DES, matched with 2570 patients treated with bare-metal stents; there were 1298 matched pairs for the STEMI group and 1228 matched pairs for the non-STEMI group.

As Mauri et al report, risk-adjusted mortality rates in the propensity-score-matched analysis were significantly lower among all patients with AMI, in all patients with STEMI, and in all patients with non-STEMI. Risk-adjusted rates of repeat MI were significantly reduced among non-STEMI patients, but differences did not reach statistical significance in the all-MI and STEMI groups. As might be expected, repeat-revascularization rates were also significantly lower in DES-treated subjects, across all MI groups, an absolute risk reduction that ranged from a mean of 3.8% to 5.5%.

As the authors note in the paper, at least two studies have suggested that DES may reduce mortality by reducing the risks associated with restenosis and repeat procedures—an effect that might "offset" the increased risk of stent thrombosis (and affiliated death/MI) associated with DES. But Mauri et al point out that in their analysis some of the benefits of DES emerged within the first six months, before any effect on reducing restenosis might have been seen.

"This result suggests that additional factors, such as the duration of dual antiplatelet therapy, which is known to provide benefit in acute coronary syndromes, might have a role," they write. While their study could not address the question of dual antiplatelet therapy duration, the period studied predated the current recommendations of 12 months, such that patients in the Massachusetts registry likely received just one month of dual antiplatelet therapy following bare-metal-stent implantation and three to six months following DES placement.

As some experts commented when Mauri first presented these results last March, interventionalists will likely be reassured by the findings, particularly since 2007 was dominated by fears that DES might actually increase the risk of death and MI, perhaps even more so in patients with thrombotic occlusions. Indeed, as Mauri et al acknowledged: "The primary purpose of our analysis was to determine whether there was any harm associated with the use of drug-eluting stents as compared with bare-metal stents in an unselected population of patients with myocardial infarction. The observation of a reduction in mortality rates with drug-eluting stents was unanticipated and merits confirmation in randomized trials."

When Mauri first presented the results, Dr Bruce Brodie (University of North Carolina, Greensboro) emphasized the difficulty of eliminating bias in an observational study, pointing out: "Bare-metal stents are put into sicker patients, patients with severe comorbidities, who are not compliant not only with dual antiplatelet agents but also with other therapies and statins. There's a real bias in this and other registries that can't be accounted for by statistical adjustments."

In response, Mauri acknowledged that while any observational study can have some "residual confounding," she thinks the principal findings of the Massachusetts registry hold true. "We believe that the degree of residual confounding is not likely to be large enough to change the conclusions of our study," she told heartwire. "Nonetheless, it will be interesting to see whether the HORIZONS randomized trial, particularly in follow-up beyond the primary end point, shows similar findings of long-term benefit of DES in AMI."

The HORIZONS-AMI trial is slated for presentation at the upcoming TCT meeting next month. HORIZONS included only Taxus paclitaxel-eluting stents, vs bare-metal stents; to heartwire, Mauri emphasized that the majority of patients in the Massachusetts registry were treated with the Cypher. Another AMI trial, the ZEST-AMI trial, is also among the TCT late-breakers; it is comparing the Cypher, the Taxus, and the Endeavor for the treatment of AMI but does not include a bare-metal-stent arm.